1 Setup

library(tidyverse)
## ── Attaching core tidyverse packages ──────────────────────── tidyverse 2.0.0 ──
## ✔ dplyr     1.1.4     ✔ readr     2.1.5
## ✔ forcats   1.0.0     ✔ stringr   1.5.1
## ✔ ggplot2   3.5.1     ✔ tibble    3.2.1
## ✔ lubridate 1.9.3     ✔ tidyr     1.3.1
## ✔ purrr     1.0.2     
## ── Conflicts ────────────────────────────────────────── tidyverse_conflicts() ──
## ✖ dplyr::filter() masks stats::filter()
## ✖ dplyr::lag()    masks stats::lag()
## ℹ Use the conflicted package (<http://conflicted.r-lib.org/>) to force all conflicts to become errors
library(readxl)
library(qiime2R)
library(vegan)
## Loading required package: permute
## Loading required package: lattice
## This is vegan 2.6-6.1
library(ape)
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## Attaching package: 'ape'
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##     where
library(ALDEx2)
## Loading required package: zCompositions
## Loading required package: MASS
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## Attaching package: 'MASS'
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##     select
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## Loading required package: NADA
## Loading required package: survival
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## Loading required package: Rfast
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## Attaching package: 'RcppParallel'
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## Attaching package: 'Rfast'
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library(rbiom)
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## Attaching package: 'rbiom'
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##     select
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library(picante)
## Loading required package: nlme
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## Attaching package: 'nlme'
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##     collapse
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## Attaching package: 'picante'
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##     unifrac
#Set working directory
setwd("/home/jjz5561/BRB_Mar2024/CAPR_computation/")
getwd()
## [1] "/home/jjz5561/BRB_Mar2024/CAPR_computation"
sessionInfo()
## R version 4.4.1 (2024-06-14)
## Platform: x86_64-pc-linux-gnu
## Running under: Ubuntu 20.04.6 LTS
## 
## Matrix products: default
## BLAS:   /usr/lib/x86_64-linux-gnu/blas/libblas.so.3.9.0 
## LAPACK: /usr/lib/x86_64-linux-gnu/lapack/liblapack.so.3.9.0
## 
## locale:
##  [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
##  [3] LC_TIME=en_US.UTF-8        LC_COLLATE=en_US.UTF-8    
##  [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
##  [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
##  [9] LC_ADDRESS=C               LC_TELEPHONE=C            
## [11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       
## 
## time zone: America/New_York
## tzcode source: system (glibc)
## 
## attached base packages:
## [1] stats     graphics  grDevices utils     datasets  methods   base     
## 
## other attached packages:
##  [1] picante_1.8.2         nlme_3.1-166          rbiom_1.0.3          
##  [4] ALDEx2_1.24.0         Rfast_2.1.0           RcppParallel_5.1.8   
##  [7] RcppZiggurat_0.1.6    Rcpp_1.0.13           zCompositions_1.5.0-4
## [10] truncnorm_1.0-9       NADA_1.6-1.1          survival_3.7-0       
## [13] MASS_7.3-61           ape_5.8               vegan_2.6-6.1        
## [16] lattice_0.22-6        permute_0.9-7         qiime2R_0.99.6       
## [19] readxl_1.4.3          lubridate_1.9.3       forcats_1.0.0        
## [22] stringr_1.5.1         dplyr_1.1.4           purrr_1.0.2          
## [25] readr_2.1.5           tidyr_1.3.1           tibble_3.2.1         
## [28] ggplot2_3.5.1         tidyverse_2.0.0      
## 
## loaded via a namespace (and not attached):
##  [1] gridExtra_2.3               rlang_1.1.4                
##  [3] magrittr_2.0.3              ade4_1.7-22                
##  [5] matrixStats_1.3.0           compiler_4.4.1             
##  [7] mgcv_1.9-1                  vctrs_0.6.5                
##  [9] reshape2_1.4.4              pkgconfig_2.0.3            
## [11] crayon_1.5.3                fastmap_1.2.0              
## [13] backports_1.5.0             XVector_0.44.0             
## [15] utf8_1.2.4                  rmarkdown_2.27             
## [17] tzdb_0.4.0                  UCSC.utils_1.0.0           
## [19] xfun_0.46                   zlibbioc_1.50.0            
## [21] cachem_1.1.0                GenomeInfoDb_1.40.1        
## [23] jsonlite_1.8.8              biomformat_1.32.0          
## [25] DelayedArray_0.30.1         rhdf5filters_1.16.0        
## [27] BiocParallel_1.38.0         Rhdf5lib_1.26.0            
## [29] parallel_4.4.1              cluster_2.1.6              
## [31] R6_2.5.1                    bslib_0.8.0                
## [33] stringi_1.8.4               rpart_4.1.23               
## [35] GenomicRanges_1.56.1        jquerylib_0.1.4            
## [37] cellranger_1.1.0            SummarizedExperiment_1.34.0
## [39] iterators_1.0.14            knitr_1.48                 
## [41] base64enc_0.1-3             IRanges_2.38.1             
## [43] Matrix_1.7-0                splines_4.4.1              
## [45] nnet_7.3-19                 igraph_2.0.3               
## [47] timechange_0.3.0            tidyselect_1.2.1           
## [49] abind_1.4-5                 rstudioapi_0.16.0          
## [51] yaml_2.3.10                 codetools_0.2-20           
## [53] plyr_1.8.9                  Biobase_2.64.0             
## [55] withr_3.0.1                 evaluate_0.24.0            
## [57] foreign_0.8-86              Biostrings_2.72.1          
## [59] pillar_1.9.0                phyloseq_1.48.0            
## [61] MatrixGenerics_1.16.0       checkmate_2.3.2            
## [63] DT_0.33                     foreach_1.5.2              
## [65] stats4_4.4.1                generics_0.1.3             
## [67] S4Vectors_0.42.1            hms_1.1.3                  
## [69] munsell_0.5.1               scales_1.3.0               
## [71] slam_0.1-52                 glue_1.7.0                 
## [73] Hmisc_5.1-3                 tools_4.4.1                
## [75] data.table_1.15.4           rhdf5_2.48.0               
## [77] grid_4.4.1                  colorspace_2.1-1           
## [79] GenomeInfoDbData_1.2.12     htmlTable_2.4.3            
## [81] Formula_1.2-5               cli_3.6.3                  
## [83] fansi_1.0.6                 S4Arrays_1.4.1             
## [85] gtable_0.3.5                sass_0.4.9                 
## [87] digest_0.6.36               BiocGenerics_0.50.0        
## [89] SparseArray_1.4.8           htmlwidgets_1.6.4          
## [91] htmltools_0.5.8.1           multtest_2.60.0            
## [93] lifecycle_1.0.4             httr_1.4.7
theme_set(theme_q2r())

1.1 Citation Information

This will be automatically generated based on the libraries loaded.

packages_in_use <- c( sessionInfo()$basePkgs, names( sessionInfo()$loadedOnly ) )
lapply( X=packages_in_use, FUN=citation) %>%
  print()
## [[1]]
## The 'stats' package is part of R.  To cite R in publications use:
## 
##   R Core Team (2024). _R: A Language and Environment for Statistical
##   Computing_. R Foundation for Statistical Computing, Vienna, Austria.
##   <https://www.R-project.org/>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {R: A Language and Environment for Statistical Computing},
##     author = {{R Core Team}},
##     organization = {R Foundation for Statistical Computing},
##     address = {Vienna, Austria},
##     year = {2024},
##     url = {https://www.R-project.org/},
##   }
## 
## We have invested a lot of time and effort in creating R, please cite it
## when using it for data analysis. See also 'citation("pkgname")' for
## citing R packages.
## 
## [[2]]
## The 'graphics' package is part of R.  To cite R in publications use:
## 
##   R Core Team (2024). _R: A Language and Environment for Statistical
##   Computing_. R Foundation for Statistical Computing, Vienna, Austria.
##   <https://www.R-project.org/>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {R: A Language and Environment for Statistical Computing},
##     author = {{R Core Team}},
##     organization = {R Foundation for Statistical Computing},
##     address = {Vienna, Austria},
##     year = {2024},
##     url = {https://www.R-project.org/},
##   }
## 
## We have invested a lot of time and effort in creating R, please cite it
## when using it for data analysis. See also 'citation("pkgname")' for
## citing R packages.
## 
## [[3]]
## The 'grDevices' package is part of R.  To cite R in publications use:
## 
##   R Core Team (2024). _R: A Language and Environment for Statistical
##   Computing_. R Foundation for Statistical Computing, Vienna, Austria.
##   <https://www.R-project.org/>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {R: A Language and Environment for Statistical Computing},
##     author = {{R Core Team}},
##     organization = {R Foundation for Statistical Computing},
##     address = {Vienna, Austria},
##     year = {2024},
##     url = {https://www.R-project.org/},
##   }
## 
## We have invested a lot of time and effort in creating R, please cite it
## when using it for data analysis. See also 'citation("pkgname")' for
## citing R packages.
## 
## [[4]]
## The 'utils' package is part of R.  To cite R in publications use:
## 
##   R Core Team (2024). _R: A Language and Environment for Statistical
##   Computing_. R Foundation for Statistical Computing, Vienna, Austria.
##   <https://www.R-project.org/>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {R: A Language and Environment for Statistical Computing},
##     author = {{R Core Team}},
##     organization = {R Foundation for Statistical Computing},
##     address = {Vienna, Austria},
##     year = {2024},
##     url = {https://www.R-project.org/},
##   }
## 
## We have invested a lot of time and effort in creating R, please cite it
## when using it for data analysis. See also 'citation("pkgname")' for
## citing R packages.
## 
## [[5]]
## The 'datasets' package is part of R.  To cite R in publications use:
## 
##   R Core Team (2024). _R: A Language and Environment for Statistical
##   Computing_. R Foundation for Statistical Computing, Vienna, Austria.
##   <https://www.R-project.org/>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {R: A Language and Environment for Statistical Computing},
##     author = {{R Core Team}},
##     organization = {R Foundation for Statistical Computing},
##     address = {Vienna, Austria},
##     year = {2024},
##     url = {https://www.R-project.org/},
##   }
## 
## We have invested a lot of time and effort in creating R, please cite it
## when using it for data analysis. See also 'citation("pkgname")' for
## citing R packages.
## 
## [[6]]
## The 'methods' package is part of R.  To cite R in publications use:
## 
##   R Core Team (2024). _R: A Language and Environment for Statistical
##   Computing_. R Foundation for Statistical Computing, Vienna, Austria.
##   <https://www.R-project.org/>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {R: A Language and Environment for Statistical Computing},
##     author = {{R Core Team}},
##     organization = {R Foundation for Statistical Computing},
##     address = {Vienna, Austria},
##     year = {2024},
##     url = {https://www.R-project.org/},
##   }
## 
## We have invested a lot of time and effort in creating R, please cite it
## when using it for data analysis. See also 'citation("pkgname")' for
## citing R packages.
## 
## [[7]]
## To cite R in publications use:
## 
##   R Core Team (2024). _R: A Language and Environment for Statistical
##   Computing_. R Foundation for Statistical Computing, Vienna, Austria.
##   <https://www.R-project.org/>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {R: A Language and Environment for Statistical Computing},
##     author = {{R Core Team}},
##     organization = {R Foundation for Statistical Computing},
##     address = {Vienna, Austria},
##     year = {2024},
##     url = {https://www.R-project.org/},
##   }
## 
## We have invested a lot of time and effort in creating R, please cite it
## when using it for data analysis. See also 'citation("pkgname")' for
## citing R packages.
## 
## [[8]]
## To cite package 'gridExtra' in publications use:
## 
##   Auguie B (2017). _gridExtra: Miscellaneous Functions for "Grid"
##   Graphics_. R package version 2.3,
##   <https://CRAN.R-project.org/package=gridExtra>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {gridExtra: Miscellaneous Functions for "Grid" Graphics},
##     author = {Baptiste Auguie},
##     year = {2017},
##     note = {R package version 2.3},
##     url = {https://CRAN.R-project.org/package=gridExtra},
##   }
## 
## [[9]]
## To cite package 'rlang' in publications use:
## 
##   Henry L, Wickham H (2024). _rlang: Functions for Base Types and Core
##   R and 'Tidyverse' Features_. R package version 1.1.4,
##   <https://CRAN.R-project.org/package=rlang>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {rlang: Functions for Base Types and Core R and 'Tidyverse' Features},
##     author = {Lionel Henry and Hadley Wickham},
##     year = {2024},
##     note = {R package version 1.1.4},
##     url = {https://CRAN.R-project.org/package=rlang},
##   }
## 
## [[10]]
## To cite package 'magrittr' in publications use:
## 
##   Bache S, Wickham H (2022). _magrittr: A Forward-Pipe Operator for R_.
##   R package version 2.0.3,
##   <https://CRAN.R-project.org/package=magrittr>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {magrittr: A Forward-Pipe Operator for R},
##     author = {Stefan Milton Bache and Hadley Wickham},
##     year = {2022},
##     note = {R package version 2.0.3},
##     url = {https://CRAN.R-project.org/package=magrittr},
##   }
## 
## [[11]]
## To cite ade4 in publications use:
## 
##   Dray S, Dufour A (2007). "The ade4 Package: Implementing the Duality
##   Diagram for Ecologists." _Journal of Statistical Software_, *22*(4),
##   1-20. doi:10.18637/jss.v022.i04
##   <https://doi.org/10.18637/jss.v022.i04>.
## 
## Bougeard S, Dray S (2018). "Supervised Multiblock Analysis in R with
## the ade4 Package." _Journal of Statistical Software_, *86*(1), 1-17.
## doi:10.18637/jss.v086.i01 <https://doi.org/10.18637/jss.v086.i01>.
## 
## Chessel D, Dufour A, Thioulouse J (2004). "The ade4 Package - I:
## One-Table Methods." _R News_, *4*(1), 5-10.
## <https://cran.r-project.org/doc/Rnews/>.
## 
## Dray S, Dufour A, Chessel D (2007). "The ade4 Package - II: Two-Table
## and K-Table Methods." _R News_, *7*(2), 47-52.
## <https://cran.r-project.org/doc/Rnews/>.
## 
## Thioulouse J, Dray S, Dufour A, Siberchicot A, Jombart T, Pavoine S
## (2018). _Multivariate Analysis of Ecological Data with ade4_. Springer.
## doi:10.1007/978-1-4939-8850-1
## <https://doi.org/10.1007/978-1-4939-8850-1>.
## 
## To see these entries in BibTeX format, use 'print(<citation>,
## bibtex=TRUE)', 'toBibtex(.)', or set
## 'options(citation.bibtex.max=999)'.
## 
## [[12]]
## To cite package 'matrixStats' in publications use:
## 
##   Bengtsson H (2024). _matrixStats: Functions that Apply to Rows and
##   Columns of Matrices (and to Vectors)_. R package version 1.3.0,
##   <https://CRAN.R-project.org/package=matrixStats>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {matrixStats: Functions that Apply to Rows and Columns of Matrices (and to
## Vectors)},
##     author = {Henrik Bengtsson},
##     year = {2024},
##     note = {R package version 1.3.0},
##     url = {https://CRAN.R-project.org/package=matrixStats},
##   }
## 
## [[13]]
## The 'compiler' package is part of R.  To cite R in publications use:
## 
##   R Core Team (2024). _R: A Language and Environment for Statistical
##   Computing_. R Foundation for Statistical Computing, Vienna, Austria.
##   <https://www.R-project.org/>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {R: A Language and Environment for Statistical Computing},
##     author = {{R Core Team}},
##     organization = {R Foundation for Statistical Computing},
##     address = {Vienna, Austria},
##     year = {2024},
##     url = {https://www.R-project.org/},
##   }
## 
## We have invested a lot of time and effort in creating R, please cite it
## when using it for data analysis. See also 'citation("pkgname")' for
## citing R packages.
## 
## [[14]]
## 2011 for generalized additive model method; 2016 for beyond exponential
## family; 2004 for strictly additive GCV based model method and basics of
## gamm; 2017 for overview; 2003 for thin plate regression splines.
## 
##   Wood, S.N. (2011) Fast stable restricted maximum likelihood and
##   marginal likelihood estimation of semiparametric generalized linear
##   models. Journal of the Royal Statistical Society (B) 73(1):3-36
## 
##   Wood S.N., N. Pya and B. Saefken (2016) Smoothing parameter and model
##   selection for general smooth models (with discussion). Journal of the
##   American Statistical Association 111:1548-1575.
## 
##   Wood, S.N. (2004) Stable and efficient multiple smoothing parameter
##   estimation for generalized additive models. Journal of the American
##   Statistical Association. 99:673-686.
## 
##   Wood, S.N. (2017) Generalized Additive Models: An Introduction with R
##   (2nd edition). Chapman and Hall/CRC.
## 
##   Wood, S.N. (2003) Thin-plate regression splines. Journal of the Royal
##   Statistical Society (B) 65(1):95-114.
## 
## To see these entries in BibTeX format, use 'print(<citation>,
## bibtex=TRUE)', 'toBibtex(.)', or set
## 'options(citation.bibtex.max=999)'.
## 
## [[15]]
## To cite package 'vctrs' in publications use:
## 
##   Wickham H, Henry L, Vaughan D (2023). _vctrs: Vector Helpers_. R
##   package version 0.6.5, <https://CRAN.R-project.org/package=vctrs>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {vctrs: Vector Helpers},
##     author = {Hadley Wickham and Lionel Henry and Davis Vaughan},
##     year = {2023},
##     note = {R package version 0.6.5},
##     url = {https://CRAN.R-project.org/package=vctrs},
##   }
## 
## [[16]]
## To cite reshape2 in publications use:
## 
##   Hadley Wickham (2007). Reshaping Data with the reshape Package.
##   Journal of Statistical Software, 21(12), 1-20. URL
##   http://www.jstatsoft.org/v21/i12/.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Article{,
##     title = {Reshaping Data with the {reshape} Package},
##     author = {Hadley Wickham},
##     journal = {Journal of Statistical Software},
##     year = {2007},
##     volume = {21},
##     number = {12},
##     pages = {1--20},
##     url = {http://www.jstatsoft.org/v21/i12/},
##   }
## 
## [[17]]
## To cite package 'pkgconfig' in publications use:
## 
##   Csárdi G (2019). _pkgconfig: Private Configuration for 'R' Packages_.
##   R package version 2.0.3,
##   <https://CRAN.R-project.org/package=pkgconfig>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {pkgconfig: Private Configuration for 'R' Packages},
##     author = {Gábor Csárdi},
##     year = {2019},
##     note = {R package version 2.0.3},
##     url = {https://CRAN.R-project.org/package=pkgconfig},
##   }
## 
## ATTENTION: This citation information has been auto-generated from the
## package DESCRIPTION file and may need manual editing, see
## 'help("citation")'.
## 
## [[18]]
## To cite package 'crayon' in publications use:
## 
##   Csárdi G (2024). _crayon: Colored Terminal Output_. R package version
##   1.5.3, <https://CRAN.R-project.org/package=crayon>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {crayon: Colored Terminal Output},
##     author = {Gábor Csárdi},
##     year = {2024},
##     note = {R package version 1.5.3},
##     url = {https://CRAN.R-project.org/package=crayon},
##   }
## 
## [[19]]
## To cite package 'fastmap' in publications use:
## 
##   Chang W (2024). _fastmap: Fast Data Structures_. R package version
##   1.2.0, <https://CRAN.R-project.org/package=fastmap>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {fastmap: Fast Data Structures},
##     author = {Winston Chang},
##     year = {2024},
##     note = {R package version 1.2.0},
##     url = {https://CRAN.R-project.org/package=fastmap},
##   }
## 
## [[20]]
## To cite package 'backports' in publications use:
## 
##   Lang M, Murdoch D, R Core Team (2024). _backports: Reimplementations
##   of Functions Introduced Since R-3.0.0_. R package version 1.5.0,
##   <https://CRAN.R-project.org/package=backports>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {backports: Reimplementations of Functions Introduced Since R-3.0.0},
##     author = {Michel Lang and Duncan Murdoch and {R Core Team}},
##     year = {2024},
##     note = {R package version 1.5.0},
##     url = {https://CRAN.R-project.org/package=backports},
##   }
## 
## [[21]]
## To cite package 'XVector' in publications use:
## 
##   Pagès H, Aboyoun P (2024). _XVector: Foundation of external vector
##   representation and manipulation in Bioconductor_.
##   doi:10.18129/B9.bioc.XVector
##   <https://doi.org/10.18129/B9.bioc.XVector>, R package version 0.44.0,
##   <https://bioconductor.org/packages/XVector>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {XVector: Foundation of external vector representation and manipulation in
## Bioconductor},
##     author = {Hervé Pagès and Patrick Aboyoun},
##     year = {2024},
##     note = {R package version 0.44.0},
##     url = {https://bioconductor.org/packages/XVector},
##     doi = {10.18129/B9.bioc.XVector},
##   }
## 
## ATTENTION: This citation information has been auto-generated from the
## package DESCRIPTION file and may need manual editing, see
## 'help("citation")'.
## 
## [[22]]
## To cite package 'utf8' in publications use:
## 
##   Perry PO (2023). _utf8: Unicode Text Processing_. R package version
##   1.2.4, <https://CRAN.R-project.org/package=utf8>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {utf8: Unicode Text Processing},
##     author = {Patrick O. Perry},
##     year = {2023},
##     note = {R package version 1.2.4},
##     url = {https://CRAN.R-project.org/package=utf8},
##   }
## 
## [[23]]
## To cite package 'rmarkdown' in publications use:
## 
##   Allaire J, Xie Y, Dervieux C, McPherson J, Luraschi J, Ushey K,
##   Atkins A, Wickham H, Cheng J, Chang W, Iannone R (2024). _rmarkdown:
##   Dynamic Documents for R_. R package version 2.27,
##   <https://github.com/rstudio/rmarkdown>.
## 
##   Xie Y, Allaire J, Grolemund G (2018). _R Markdown: The Definitive
##   Guide_. Chapman and Hall/CRC, Boca Raton, Florida. ISBN
##   9781138359338, <https://bookdown.org/yihui/rmarkdown>.
## 
##   Xie Y, Dervieux C, Riederer E (2020). _R Markdown Cookbook_. Chapman
##   and Hall/CRC, Boca Raton, Florida. ISBN 9780367563837,
##   <https://bookdown.org/yihui/rmarkdown-cookbook>.
## 
## To see these entries in BibTeX format, use 'print(<citation>,
## bibtex=TRUE)', 'toBibtex(.)', or set
## 'options(citation.bibtex.max=999)'.
## 
## [[24]]
## To cite package 'tzdb' in publications use:
## 
##   Vaughan D (2023). _tzdb: Time Zone Database Information_. R package
##   version 0.4.0, <https://CRAN.R-project.org/package=tzdb>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {tzdb: Time Zone Database Information},
##     author = {Davis Vaughan},
##     year = {2023},
##     note = {R package version 0.4.0},
##     url = {https://CRAN.R-project.org/package=tzdb},
##   }
## 
## [[25]]
## To cite package 'UCSC.utils' in publications use:
## 
##   Pagès H (2024). _UCSC.utils: Low-level utilities to retrieve data
##   from the UCSC Genome Browser_. doi:10.18129/B9.bioc.UCSC.utils
##   <https://doi.org/10.18129/B9.bioc.UCSC.utils>, R package version
##   1.0.0, <https://bioconductor.org/packages/UCSC.utils>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {UCSC.utils: Low-level utilities to retrieve data from the UCSC Genome
## Browser},
##     author = {Hervé Pagès},
##     year = {2024},
##     note = {R package version 1.0.0},
##     url = {https://bioconductor.org/packages/UCSC.utils},
##     doi = {10.18129/B9.bioc.UCSC.utils},
##   }
## 
## [[26]]
## To cite package 'xfun' in publications use:
## 
##   Xie Y (2024). _xfun: Supporting Functions for Packages Maintained by
##   'Yihui Xie'_. R package version 0.46,
##   <https://CRAN.R-project.org/package=xfun>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {xfun: Supporting Functions for Packages Maintained by 'Yihui Xie'},
##     author = {Yihui Xie},
##     year = {2024},
##     note = {R package version 0.46},
##     url = {https://CRAN.R-project.org/package=xfun},
##   }
## 
## [[27]]
## To cite package 'zlibbioc' in publications use:
## 
##   Morgan M (2024). _zlibbioc: An R packaged zlib-1.2.5_.
##   doi:10.18129/B9.bioc.zlibbioc
##   <https://doi.org/10.18129/B9.bioc.zlibbioc>, R package version
##   1.50.0, <https://bioconductor.org/packages/zlibbioc>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {zlibbioc: An R packaged zlib-1.2.5},
##     author = {Martin Morgan},
##     year = {2024},
##     note = {R package version 1.50.0},
##     url = {https://bioconductor.org/packages/zlibbioc},
##     doi = {10.18129/B9.bioc.zlibbioc},
##   }
## 
## ATTENTION: This citation information has been auto-generated from the
## package DESCRIPTION file and may need manual editing, see
## 'help("citation")'.
## 
## [[28]]
## To cite package 'cachem' in publications use:
## 
##   Chang W (2024). _cachem: Cache R Objects with Automatic Pruning_. R
##   package version 1.1.0, <https://CRAN.R-project.org/package=cachem>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {cachem: Cache R Objects with Automatic Pruning},
##     author = {Winston Chang},
##     year = {2024},
##     note = {R package version 1.1.0},
##     url = {https://CRAN.R-project.org/package=cachem},
##   }
## 
## [[29]]
## To cite package 'GenomeInfoDb' in publications use:
## 
##   Arora S, Morgan M, Carlson M, Pagès H (2024). _GenomeInfoDb:
##   Utilities for manipulating chromosome names, including modifying them
##   to follow a particular naming style_.
##   doi:10.18129/B9.bioc.GenomeInfoDb
##   <https://doi.org/10.18129/B9.bioc.GenomeInfoDb>, R package version
##   1.40.1, <https://bioconductor.org/packages/GenomeInfoDb>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {GenomeInfoDb: Utilities for manipulating chromosome names, including modifying
## them to follow a particular naming style},
##     author = {Sonali Arora and Martin Morgan and Marc Carlson and Hervé Pagès},
##     year = {2024},
##     note = {R package version 1.40.1},
##     url = {https://bioconductor.org/packages/GenomeInfoDb},
##     doi = {10.18129/B9.bioc.GenomeInfoDb},
##   }
## 
## [[30]]
## To cite jsonlite in publications use:
## 
##   Ooms J (2014). "The jsonlite Package: A Practical and Consistent
##   Mapping Between JSON Data and R Objects." _arXiv:1403.2805
##   [stat.CO]_. <https://arxiv.org/abs/1403.2805>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Article{,
##     title = {The jsonlite Package: A Practical and Consistent Mapping Between JSON Data and R Objects},
##     author = {Jeroen Ooms},
##     journal = {arXiv:1403.2805 [stat.CO]},
##     year = {2014},
##     url = {https://arxiv.org/abs/1403.2805},
##   }
## 
## [[31]]
## To cite package 'biomformat' in publications use:
## 
##   McMurdie PJ, Paulson JN (2024). _biomformat: An interface package for
##   the BIOM file format_. doi:10.18129/B9.bioc.biomformat
##   <https://doi.org/10.18129/B9.bioc.biomformat>, R package version
##   1.32.0, <https://bioconductor.org/packages/biomformat>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {biomformat: An interface package for the BIOM file format},
##     author = {Paul J. McMurdie and Joseph N Paulson},
##     year = {2024},
##     note = {R package version 1.32.0},
##     url = {https://bioconductor.org/packages/biomformat},
##     doi = {10.18129/B9.bioc.biomformat},
##   }
## 
## ATTENTION: This citation information has been auto-generated from the
## package DESCRIPTION file and may need manual editing, see
## 'help("citation")'.
## 
## [[32]]
## To cite package 'DelayedArray' in publications use:
## 
##   Pagès H (2024). _DelayedArray: A unified framework for working
##   transparently with on-disk and in-memory array-like datasets_.
##   doi:10.18129/B9.bioc.DelayedArray
##   <https://doi.org/10.18129/B9.bioc.DelayedArray>, R package version
##   0.30.1, <https://bioconductor.org/packages/DelayedArray>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {DelayedArray: A unified framework for working transparently with on-disk and
## in-memory array-like datasets},
##     author = {Hervé Pagès},
##     year = {2024},
##     note = {R package version 0.30.1},
##     url = {https://bioconductor.org/packages/DelayedArray},
##     doi = {10.18129/B9.bioc.DelayedArray},
##   }
## 
## [[33]]
## To cite package 'rhdf5filters' in publications use:
## 
##   Smith M (2024). _rhdf5filters: HDF5 Compression Filters_.
##   doi:10.18129/B9.bioc.rhdf5filters
##   <https://doi.org/10.18129/B9.bioc.rhdf5filters>, R package version
##   1.16.0, <https://bioconductor.org/packages/rhdf5filters>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {rhdf5filters: HDF5 Compression Filters},
##     author = {Mike Smith},
##     year = {2024},
##     note = {R package version 1.16.0},
##     url = {https://bioconductor.org/packages/rhdf5filters},
##     doi = {10.18129/B9.bioc.rhdf5filters},
##   }
## 
## [[34]]
## To cite package 'BiocParallel' in publications use:
## 
##   Morgan M, Wang J, Obenchain V, Lang M, Thompson R, Turaga N (2024).
##   _BiocParallel: Bioconductor facilities for parallel evaluation_.
##   doi:10.18129/B9.bioc.BiocParallel
##   <https://doi.org/10.18129/B9.bioc.BiocParallel>, R package version
##   1.38.0, <https://bioconductor.org/packages/BiocParallel>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {BiocParallel: Bioconductor facilities for parallel evaluation},
##     author = {Martin Morgan and Jiefei Wang and Valerie Obenchain and Michel Lang and Ryan Thompson and Nitesh Turaga},
##     year = {2024},
##     note = {R package version 1.38.0},
##     url = {https://bioconductor.org/packages/BiocParallel},
##     doi = {10.18129/B9.bioc.BiocParallel},
##   }
## 
## [[35]]
## To cite package 'Rhdf5lib' in publications use:
## 
##   Smith M (2024). _Rhdf5lib: hdf5 library as an R package_.
##   doi:10.18129/B9.bioc.Rhdf5lib
##   <https://doi.org/10.18129/B9.bioc.Rhdf5lib>, R package version
##   1.26.0, <https://bioconductor.org/packages/Rhdf5lib>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {Rhdf5lib: hdf5 library as an R package},
##     author = {Mike Smith},
##     year = {2024},
##     note = {R package version 1.26.0},
##     url = {https://bioconductor.org/packages/Rhdf5lib},
##     doi = {10.18129/B9.bioc.Rhdf5lib},
##   }
## 
## [[36]]
## The 'parallel' package is part of R.  To cite R in publications use:
## 
##   R Core Team (2024). _R: A Language and Environment for Statistical
##   Computing_. R Foundation for Statistical Computing, Vienna, Austria.
##   <https://www.R-project.org/>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {R: A Language and Environment for Statistical Computing},
##     author = {{R Core Team}},
##     organization = {R Foundation for Statistical Computing},
##     address = {Vienna, Austria},
##     year = {2024},
##     url = {https://www.R-project.org/},
##   }
## 
## We have invested a lot of time and effort in creating R, please cite it
## when using it for data analysis. See also 'citation("pkgname")' for
## citing R packages.
## 
## [[37]]
## To cite the R package cluster in publications use:
## 
##   Maechler, M., Rousseeuw, P., Struyf, A., Hubert, M., Hornik,
##   K.(2023).  cluster: Cluster Analysis Basics and Extensions. R package
##   version 2.1.6.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {cluster: Cluster Analysis Basics and Extensions},
##     author = {Martin Maechler and Peter Rousseeuw and Anja Struyf and Mia Hubert and Kurt Hornik},
##     year = {2023},
##     url = {https://CRAN.R-project.org/package=cluster},
##     note = {R package version 2.1.6 --- For new features, see the 'NEWS' and the 'Changelog' file in the package source)},
##   }
## 
## [[38]]
## To cite package 'R6' in publications use:
## 
##   Chang W (2021). _R6: Encapsulated Classes with Reference Semantics_.
##   R package version 2.5.1, <https://CRAN.R-project.org/package=R6>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {R6: Encapsulated Classes with Reference Semantics},
##     author = {Winston Chang},
##     year = {2021},
##     note = {R package version 2.5.1},
##     url = {https://CRAN.R-project.org/package=R6},
##   }
## 
## [[39]]
## To cite package 'bslib' in publications use:
## 
##   Sievert C, Cheng J, Aden-Buie G (2024). _bslib: Custom 'Bootstrap'
##   'Sass' Themes for 'shiny' and 'rmarkdown'_. R package version 0.8.0,
##   <https://CRAN.R-project.org/package=bslib>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {bslib: Custom 'Bootstrap' 'Sass' Themes for 'shiny' and 'rmarkdown'},
##     author = {Carson Sievert and Joe Cheng and Garrick Aden-Buie},
##     year = {2024},
##     note = {R package version 0.8.0},
##     url = {https://CRAN.R-project.org/package=bslib},
##   }
## 
## [[40]]
## To cite stringi in publications, use:
## 
##   Gagolewski M (2022). "stringi: Fast and portable character string
##   processing in R." _Journal of Statistical Software_, *103*(2), 1-59.
##   doi:10.18637/jss.v103.i02 <https://doi.org/10.18637/jss.v103.i02>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Article{,
##     title = {{stringi}: {F}ast and portable character string processing in {R}},
##     author = {Marek Gagolewski},
##     journal = {Journal of Statistical Software},
##     year = {2022},
##     volume = {103},
##     number = {2},
##     pages = {1--59},
##     doi = {10.18637/jss.v103.i02},
##   }
## 
## [[41]]
## To cite package 'rpart' in publications use:
## 
##   Therneau T, Atkinson B (2023). _rpart: Recursive Partitioning and
##   Regression Trees_. R package version 4.1.23,
##   <https://CRAN.R-project.org/package=rpart>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {rpart: Recursive Partitioning and Regression Trees},
##     author = {Terry Therneau and Beth Atkinson},
##     year = {2023},
##     note = {R package version 4.1.23},
##     url = {https://CRAN.R-project.org/package=rpart},
##   }
## 
## [[42]]
## To cite package 'GenomicRanges' in publications use:
## 
##   Lawrence M, Huber W, Pag\`es H, Aboyoun P, Carlson M, et al. (2013)
##   Software for Computing and Annotating Genomic Ranges. PLoS Comput
##   Biol 9(8): e1003118. doi:10.1371/journal.pcbi.1003118
## 
## A BibTeX entry for LaTeX users is
## 
##   @Article{,
##     title = {Software for Computing and Annotating Genomic Ranges},
##     author = {Michael Lawrence and Wolfgang Huber and Herv\'e Pag\`es and Patrick Aboyoun and Marc Carlson and Robert Gentleman and Martin Morgan and Vincent Carey},
##     year = {2013},
##     journal = {{PLoS} Computational Biology},
##     volume = {9},
##     issue = {8},
##     doi = {10.1371/journal.pcbi.1003118},
##     url = {http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1003118},
##   }
## 
## [[43]]
## To cite package 'jquerylib' in publications use:
## 
##   Sievert C, Cheng J (2021). _jquerylib: Obtain 'jQuery' as an HTML
##   Dependency Object_. R package version 0.1.4,
##   <https://CRAN.R-project.org/package=jquerylib>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {jquerylib: Obtain 'jQuery' as an HTML Dependency Object},
##     author = {Carson Sievert and Joe Cheng},
##     year = {2021},
##     note = {R package version 0.1.4},
##     url = {https://CRAN.R-project.org/package=jquerylib},
##   }
## 
## [[44]]
## To cite package 'cellranger' in publications use:
## 
##   Bryan J (2016). _cellranger: Translate Spreadsheet Cell Ranges to
##   Rows and Columns_. R package version 1.1.0,
##   <https://CRAN.R-project.org/package=cellranger>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {cellranger: Translate Spreadsheet Cell Ranges to Rows and Columns},
##     author = {Jennifer Bryan},
##     year = {2016},
##     note = {R package version 1.1.0},
##     url = {https://CRAN.R-project.org/package=cellranger},
##   }
## 
## [[45]]
## To cite package 'SummarizedExperiment' in publications use:
## 
##   Morgan M, Obenchain V, Hester J, Pagès H (2024).
##   _SummarizedExperiment: SummarizedExperiment container_.
##   doi:10.18129/B9.bioc.SummarizedExperiment
##   <https://doi.org/10.18129/B9.bioc.SummarizedExperiment>, R package
##   version 1.34.0,
##   <https://bioconductor.org/packages/SummarizedExperiment>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {SummarizedExperiment: SummarizedExperiment container},
##     author = {Martin Morgan and Valerie Obenchain and Jim Hester and Hervé Pagès},
##     year = {2024},
##     note = {R package version 1.34.0},
##     url = {https://bioconductor.org/packages/SummarizedExperiment},
##     doi = {10.18129/B9.bioc.SummarizedExperiment},
##   }
## 
## [[46]]
## To cite package 'iterators' in publications use:
## 
##   Analytics R, Weston S (2022). _iterators: Provides Iterator
##   Construct_. R package version 1.0.14,
##   <https://CRAN.R-project.org/package=iterators>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {iterators: Provides Iterator Construct},
##     author = {Revolution Analytics and Steve Weston},
##     year = {2022},
##     note = {R package version 1.0.14},
##     url = {https://CRAN.R-project.org/package=iterators},
##   }
## 
## [[47]]
## To cite package 'knitr' in publications use:
## 
##   Xie Y (2024). _knitr: A General-Purpose Package for Dynamic Report
##   Generation in R_. R package version 1.48, <https://yihui.org/knitr/>.
## 
##   Yihui Xie (2015) Dynamic Documents with R and knitr. 2nd edition.
##   Chapman and Hall/CRC. ISBN 978-1498716963
## 
##   Yihui Xie (2014) knitr: A Comprehensive Tool for Reproducible
##   Research in R. In Victoria Stodden, Friedrich Leisch and Roger D.
##   Peng, editors, Implementing Reproducible Computational Research.
##   Chapman and Hall/CRC. ISBN 978-1466561595
## 
## To see these entries in BibTeX format, use 'print(<citation>,
## bibtex=TRUE)', 'toBibtex(.)', or set
## 'options(citation.bibtex.max=999)'.
## 
## [[48]]
## To cite package 'base64enc' in publications use:
## 
##   Urbanek S (2015). _base64enc: Tools for base64 encoding_. R package
##   version 0.1-3, <https://CRAN.R-project.org/package=base64enc>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {base64enc: Tools for base64 encoding},
##     author = {Simon Urbanek},
##     year = {2015},
##     note = {R package version 0.1-3},
##     url = {https://CRAN.R-project.org/package=base64enc},
##   }
## 
## ATTENTION: This citation information has been auto-generated from the
## package DESCRIPTION file and may need manual editing, see
## 'help("citation")'.
## 
## [[49]]
## To cite package 'IRanges' in publications use:
## 
##   Lawrence M, Huber W, Pag\`es H, Aboyoun P, Carlson M, et al. (2013)
##   Software for Computing and Annotating Genomic Ranges. PLoS Comput
##   Biol 9(8): e1003118. doi:10.1371/journal.pcbi.1003118
## 
## A BibTeX entry for LaTeX users is
## 
##   @Article{,
##     title = {Software for Computing and Annotating Genomic Ranges},
##     author = {Michael Lawrence and Wolfgang Huber and Herv\'e Pag\`es and Patrick Aboyoun and Marc Carlson and Robert Gentleman and Martin Morgan and Vincent Carey},
##     year = {2013},
##     journal = {{PLoS} Computational Biology},
##     volume = {9},
##     issue = {8},
##     doi = {10.1371/journal.pcbi.1003118},
##     url = {http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1003118},
##   }
## 
## [[50]]
## To cite package 'Matrix' in publications use:
## 
##   Bates D, Maechler M, Jagan M (2024). _Matrix: Sparse and Dense Matrix
##   Classes and Methods_. R package version 1.7-0,
##   <https://CRAN.R-project.org/package=Matrix>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {Matrix: Sparse and Dense Matrix Classes and Methods},
##     author = {Douglas Bates and Martin Maechler and Mikael Jagan},
##     year = {2024},
##     note = {R package version 1.7-0},
##     url = {https://CRAN.R-project.org/package=Matrix},
##   }
## 
## [[51]]
## The 'splines' package is part of R.  To cite R in publications use:
## 
##   R Core Team (2024). _R: A Language and Environment for Statistical
##   Computing_. R Foundation for Statistical Computing, Vienna, Austria.
##   <https://www.R-project.org/>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {R: A Language and Environment for Statistical Computing},
##     author = {{R Core Team}},
##     organization = {R Foundation for Statistical Computing},
##     address = {Vienna, Austria},
##     year = {2024},
##     url = {https://www.R-project.org/},
##   }
## 
## We have invested a lot of time and effort in creating R, please cite it
## when using it for data analysis. See also 'citation("pkgname")' for
## citing R packages.
## 
## [[52]]
## To cite the nnet package in publications use:
## 
##   Venables, W. N. & Ripley, B. D. (2002) Modern Applied Statistics with
##   S. Fourth Edition. Springer, New York. ISBN 0-387-95457-0
## 
## A BibTeX entry for LaTeX users is
## 
##   @Book{,
##     title = {Modern Applied Statistics with S},
##     author = {W. N. Venables and B. D. Ripley},
##     publisher = {Springer},
##     edition = {Fourth},
##     address = {New York},
##     year = {2002},
##     note = {ISBN 0-387-95457-0},
##     url = {https://www.stats.ox.ac.uk/pub/MASS4/},
##   }
## 
## [[53]]
## To cite 'igraph' in publications use:
## 
##   Csardi G, Nepusz T (2006). "The igraph software package for complex
##   network research." _InterJournal_, *Complex Systems*, 1695.
##   <https://igraph.org>.
## 
## Csárdi G, Nepusz T, Traag V, Horvát Sz, Zanini F, Noom D, Müller K
## (2024). _igraph: Network Analysis and Visualization in R_.
## doi:10.5281/zenodo.7682609 <https://doi.org/10.5281/zenodo.7682609>, R
## package version 2.0.3, <https://CRAN.R-project.org/package=igraph>.
## 
## To see these entries in BibTeX format, use 'print(<citation>,
## bibtex=TRUE)', 'toBibtex(.)', or set
## 'options(citation.bibtex.max=999)'.
## 
## [[54]]
## To cite package 'timechange' in publications use:
## 
##   Spinu V (2024). _timechange: Efficient Manipulation of Date-Times_. R
##   package version 0.3.0,
##   <https://CRAN.R-project.org/package=timechange>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {timechange: Efficient Manipulation of Date-Times},
##     author = {Vitalie Spinu},
##     year = {2024},
##     note = {R package version 0.3.0},
##     url = {https://CRAN.R-project.org/package=timechange},
##   }
## 
## [[55]]
## To cite package 'tidyselect' in publications use:
## 
##   Henry L, Wickham H (2024). _tidyselect: Select from a Set of
##   Strings_. R package version 1.2.1,
##   <https://CRAN.R-project.org/package=tidyselect>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {tidyselect: Select from a Set of Strings},
##     author = {Lionel Henry and Hadley Wickham},
##     year = {2024},
##     note = {R package version 1.2.1},
##     url = {https://CRAN.R-project.org/package=tidyselect},
##   }
## 
## [[56]]
## To cite package 'abind' in publications use:
## 
##   Plate T, Heiberger R (2016). _abind: Combine Multidimensional
##   Arrays_. R package version 1.4-5,
##   <https://CRAN.R-project.org/package=abind>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {abind: Combine Multidimensional Arrays},
##     author = {Tony Plate and Richard Heiberger},
##     year = {2016},
##     note = {R package version 1.4-5},
##     url = {https://CRAN.R-project.org/package=abind},
##   }
## 
## ATTENTION: This citation information has been auto-generated from the
## package DESCRIPTION file and may need manual editing, see
## 'help("citation")'.
## 
## [[57]]
## To cite package 'rstudioapi' in publications use:
## 
##   Ushey K, Allaire J, Wickham H, Ritchie G (2024). _rstudioapi: Safely
##   Access the RStudio API_. R package version 0.16.0,
##   <https://CRAN.R-project.org/package=rstudioapi>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {rstudioapi: Safely Access the RStudio API},
##     author = {Kevin Ushey and JJ Allaire and Hadley Wickham and Gary Ritchie},
##     year = {2024},
##     note = {R package version 0.16.0},
##     url = {https://CRAN.R-project.org/package=rstudioapi},
##   }
## 
## [[58]]
## To cite package 'yaml' in publications use:
## 
##   Garbett SP, Stephens J, Simonov K, Xie Y, Dong Z, Wickham H, Horner
##   J, reikoch, Beasley W, O'Connor B, Warnes GR, Quinn M, Kamvar ZN, Gao
##   C (2024). _yaml: Methods to Convert R Data to YAML and Back_. R
##   package version 2.3.10, <https://CRAN.R-project.org/package=yaml>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {yaml: Methods to Convert R Data to YAML and Back},
##     author = {Shawn P Garbett and Jeremy Stephens and Kirill Simonov and Yihui Xie and Zhuoer Dong and Hadley Wickham and Jeffrey Horner and {reikoch} and Will Beasley and Brendan O'Connor and Gregory R. Warnes and Michael Quinn and Zhian N. Kamvar and Charlie Gao},
##     year = {2024},
##     note = {R package version 2.3.10},
##     url = {https://CRAN.R-project.org/package=yaml},
##   }
## 
## ATTENTION: This citation information has been auto-generated from the
## package DESCRIPTION file and may need manual editing, see
## 'help("citation")'.
## 
## [[59]]
## To cite package 'codetools' in publications use:
## 
##   Tierney L (2024). _codetools: Code Analysis Tools for R_. R package
##   version 0.2-20, <https://CRAN.R-project.org/package=codetools>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {codetools: Code Analysis Tools for R},
##     author = {Luke Tierney},
##     year = {2024},
##     note = {R package version 0.2-20},
##     url = {https://CRAN.R-project.org/package=codetools},
##   }
## 
## ATTENTION: This citation information has been auto-generated from the
## package DESCRIPTION file and may need manual editing, see
## 'help("citation")'.
## 
## [[60]]
## To cite package 'plyr' in publications use:
## 
##   Hadley Wickham (2011). The Split-Apply-Combine Strategy for Data
##   Analysis. Journal of Statistical Software, 40(1), 1-29. URL
##   https://www.jstatsoft.org/v40/i01/.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Article{,
##     title = {The Split-Apply-Combine Strategy for Data Analysis},
##     author = {Hadley Wickham},
##     journal = {Journal of Statistical Software},
##     year = {2011},
##     volume = {40},
##     number = {1},
##     pages = {1--29},
##     url = {https://www.jstatsoft.org/v40/i01/},
##   }
## 
## [[61]]
## To cite package 'Biobase' in publications use:
## 
##   Orchestrating high-throughput genomic analysis with Bioconductor. W.
##   Huber, V.J. Carey, R. Gentleman, ..., M. Morgan Nature Methods,
##   2015:12, 115.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Article{,
##     author = {W. Huber and V. J. Carey and R. Gentleman and S. Anders and M. Carlson and B. S. Carvalho and H. C. Bravo and S. Davis and L. Gatto and T. Girke and R. Gottardo and F. Hahne and K. D. Hansen and R. A. Irizarry and M. Lawrence and M. I. Love and J. MacDonald and V. Obenchain and A. K. {Ole's} and H. {Pag`es} and A. Reyes and P. Shannon and G. K. Smyth and D. Tenenbaum and L. Waldron and M. Morgan},
##     title = {{O}rchestrating high-throughput genomic analysis with {B}ioconductor},
##     journal = {Nature Methods},
##     year = {2015},
##     volume = {12},
##     number = {2},
##     pages = {115--121},
##     url = {http://www.nature.com/nmeth/journal/v12/n2/full/nmeth.3252.html},
##   }
## 
## [[62]]
## To cite package 'withr' in publications use:
## 
##   Hester J, Henry L, Müller K, Ushey K, Wickham H, Chang W (2024).
##   _withr: Run Code 'With' Temporarily Modified Global State_. R package
##   version 3.0.1, <https://CRAN.R-project.org/package=withr>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {withr: Run Code 'With' Temporarily Modified Global State},
##     author = {Jim Hester and Lionel Henry and Kirill Müller and Kevin Ushey and Hadley Wickham and Winston Chang},
##     year = {2024},
##     note = {R package version 3.0.1},
##     url = {https://CRAN.R-project.org/package=withr},
##   }
## 
## [[63]]
## To cite package 'evaluate' in publications use:
## 
##   Wickham H, Xie Y (2024). _evaluate: Parsing and Evaluation Tools that
##   Provide More Details than the Default_. R package version 0.24.0,
##   <https://CRAN.R-project.org/package=evaluate>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {evaluate: Parsing and Evaluation Tools that Provide More Details than the
## Default},
##     author = {Hadley Wickham and Yihui Xie},
##     year = {2024},
##     note = {R package version 0.24.0},
##     url = {https://CRAN.R-project.org/package=evaluate},
##   }
## 
## [[64]]
## To cite package 'foreign' in publications use:
## 
##   R Core Team (2023). _foreign: Read Data Stored by 'Minitab', 'S',
##   'SAS', 'SPSS', 'Stata', 'Systat', 'Weka', 'dBase', ..._. R package
##   version 0.8-86, <https://CRAN.R-project.org/package=foreign>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {foreign: Read Data Stored by 'Minitab', 'S', 'SAS', 'SPSS', 'Stata',
## 'Systat', 'Weka', 'dBase', ...},
##     author = {{R Core Team}},
##     year = {2023},
##     note = {R package version 0.8-86},
##     url = {https://CRAN.R-project.org/package=foreign},
##   }
## 
## [[65]]
## To cite package 'Biostrings' in publications use:
## 
##   Pagès H, Aboyoun P, Gentleman R, DebRoy S (2024). _Biostrings:
##   Efficient manipulation of biological strings_.
##   doi:10.18129/B9.bioc.Biostrings
##   <https://doi.org/10.18129/B9.bioc.Biostrings>, R package version
##   2.72.1, <https://bioconductor.org/packages/Biostrings>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {Biostrings: Efficient manipulation of biological strings},
##     author = {Hervé Pagès and Patrick Aboyoun and Robert Gentleman and Saikat DebRoy},
##     year = {2024},
##     note = {R package version 2.72.1},
##     url = {https://bioconductor.org/packages/Biostrings},
##     doi = {10.18129/B9.bioc.Biostrings},
##   }
## 
## [[66]]
## To cite package 'pillar' in publications use:
## 
##   Müller K, Wickham H (2023). _pillar: Coloured Formatting for
##   Columns_. R package version 1.9.0,
##   <https://CRAN.R-project.org/package=pillar>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {pillar: Coloured Formatting for Columns},
##     author = {Kirill Müller and Hadley Wickham},
##     year = {2023},
##     note = {R package version 1.9.0},
##     url = {https://CRAN.R-project.org/package=pillar},
##   }
## 
## [[67]]
## To cite phyloseq in publications, or otherwise credit, please use:
## 
##   phyloseq: An R package for reproducible interactive analysis and
##   graphics of microbiome census data. Paul J. McMurdie and Susan Holmes
##   (2013) PLoS ONE 8(4):e61217.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Article{,
##     author = {Paul J. McMurdie and Susan Holmes},
##     journal = {PLoS ONE},
##     pages = {e61217},
##     title = {phyloseq: An R package for reproducible interactive analysis and graphics of microbiome census data},
##     volume = {8},
##     number = {4},
##     year = {2013},
##     url = {http://dx.plos.org/10.1371/journal.pone.0061217},
##   }
## 
## [[68]]
## To cite package 'MatrixGenerics' in publications use:
## 
##   Ahlmann-Eltze C, Hickey P, Pagès H (2024). _MatrixGenerics: S4
##   Generic Summary Statistic Functions that Operate on Matrix-Like
##   Objects_. doi:10.18129/B9.bioc.MatrixGenerics
##   <https://doi.org/10.18129/B9.bioc.MatrixGenerics>, R package version
##   1.16.0, <https://bioconductor.org/packages/MatrixGenerics>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {MatrixGenerics: S4 Generic Summary Statistic Functions that Operate on
## Matrix-Like Objects},
##     author = {Constantin Ahlmann-Eltze and Peter Hickey and Hervé Pagès},
##     year = {2024},
##     note = {R package version 1.16.0},
##     url = {https://bioconductor.org/packages/MatrixGenerics},
##     doi = {10.18129/B9.bioc.MatrixGenerics},
##   }
## 
## [[69]]
## To cite package 'checkmate' in publications use:
## 
##   Lang M (2017). "checkmate: Fast Argument Checks for Defensive R
##   Programming." _The R Journal_, *9*(1), 437-445.
##   doi:10.32614/RJ-2017-028 <https://doi.org/10.32614/RJ-2017-028>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Article{checkmate,
##     title = {{checkmate}: Fast Argument Checks for Defensive {R} Programming},
##     author = {Michel Lang},
##     journal = {The R Journal},
##     year = {2017},
##     doi = {10.32614/RJ-2017-028},
##     pages = {437--445},
##     volume = {9},
##     number = {1},
##   }
## 
## [[70]]
## To cite package 'DT' in publications use:
## 
##   Xie Y, Cheng J, Tan X (2024). _DT: A Wrapper of the JavaScript
##   Library 'DataTables'_. R package version 0.33,
##   <https://CRAN.R-project.org/package=DT>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {DT: A Wrapper of the JavaScript Library 'DataTables'},
##     author = {Yihui Xie and Joe Cheng and Xianying Tan},
##     year = {2024},
##     note = {R package version 0.33},
##     url = {https://CRAN.R-project.org/package=DT},
##   }
## 
## [[71]]
## To cite package 'foreach' in publications use:
## 
##   Microsoft, Weston S (2022). _foreach: Provides Foreach Looping
##   Construct_. R package version 1.5.2,
##   <https://CRAN.R-project.org/package=foreach>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {foreach: Provides Foreach Looping Construct},
##     author = {{Microsoft} and Steve Weston},
##     year = {2022},
##     note = {R package version 1.5.2},
##     url = {https://CRAN.R-project.org/package=foreach},
##   }
## 
## [[72]]
## The 'stats4' package is part of R.  To cite R in publications use:
## 
##   R Core Team (2024). _R: A Language and Environment for Statistical
##   Computing_. R Foundation for Statistical Computing, Vienna, Austria.
##   <https://www.R-project.org/>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {R: A Language and Environment for Statistical Computing},
##     author = {{R Core Team}},
##     organization = {R Foundation for Statistical Computing},
##     address = {Vienna, Austria},
##     year = {2024},
##     url = {https://www.R-project.org/},
##   }
## 
## We have invested a lot of time and effort in creating R, please cite it
## when using it for data analysis. See also 'citation("pkgname")' for
## citing R packages.
## 
## [[73]]
## To cite package 'generics' in publications use:
## 
##   Wickham H, Kuhn M, Vaughan D (2022). _generics: Common S3 Generics
##   not Provided by Base R Methods Related to Model Fitting_. R package
##   version 0.1.3, <https://CRAN.R-project.org/package=generics>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {generics: Common S3 Generics not Provided by Base R Methods Related to
## Model Fitting},
##     author = {Hadley Wickham and Max Kuhn and Davis Vaughan},
##     year = {2022},
##     note = {R package version 0.1.3},
##     url = {https://CRAN.R-project.org/package=generics},
##   }
## 
## [[74]]
## To cite package 'S4Vectors' in publications use:
## 
##   Pagès H, Lawrence M, Aboyoun P (2024). _S4Vectors: Foundation of
##   vector-like and list-like containers in Bioconductor_.
##   doi:10.18129/B9.bioc.S4Vectors
##   <https://doi.org/10.18129/B9.bioc.S4Vectors>, R package version
##   0.42.1, <https://bioconductor.org/packages/S4Vectors>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {S4Vectors: Foundation of vector-like and list-like containers in
## Bioconductor},
##     author = {Hervé Pagès and Michael Lawrence and Patrick Aboyoun},
##     year = {2024},
##     note = {R package version 0.42.1},
##     url = {https://bioconductor.org/packages/S4Vectors},
##     doi = {10.18129/B9.bioc.S4Vectors},
##   }
## 
## [[75]]
## To cite package 'hms' in publications use:
## 
##   Müller K (2023). _hms: Pretty Time of Day_. R package version 1.1.3,
##   <https://CRAN.R-project.org/package=hms>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {hms: Pretty Time of Day},
##     author = {Kirill Müller},
##     year = {2023},
##     note = {R package version 1.1.3},
##     url = {https://CRAN.R-project.org/package=hms},
##   }
## 
## [[76]]
## To cite package 'munsell' in publications use:
## 
##   Wickham C (2024). _munsell: Utilities for Using Munsell Colours_. R
##   package version 0.5.1, <https://CRAN.R-project.org/package=munsell>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {munsell: Utilities for Using Munsell Colours},
##     author = {Charlotte Wickham},
##     year = {2024},
##     note = {R package version 0.5.1},
##     url = {https://CRAN.R-project.org/package=munsell},
##   }
## 
## ATTENTION: This citation information has been auto-generated from the
## package DESCRIPTION file and may need manual editing, see
## 'help("citation")'.
## 
## [[77]]
## To cite package 'scales' in publications use:
## 
##   Wickham H, Pedersen T, Seidel D (2023). _scales: Scale Functions for
##   Visualization_. R package version 1.3.0,
##   <https://CRAN.R-project.org/package=scales>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {scales: Scale Functions for Visualization},
##     author = {Hadley Wickham and Thomas Lin Pedersen and Dana Seidel},
##     year = {2023},
##     note = {R package version 1.3.0},
##     url = {https://CRAN.R-project.org/package=scales},
##   }
## 
## [[78]]
## To cite package 'slam' in publications use:
## 
##   Hornik K, Meyer D, Buchta C (2024). _slam: Sparse Lightweight Arrays
##   and Matrices_. R package version 0.1-52,
##   <https://CRAN.R-project.org/package=slam>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {slam: Sparse Lightweight Arrays and Matrices},
##     author = {Kurt Hornik and David Meyer and Christian Buchta},
##     year = {2024},
##     note = {R package version 0.1-52},
##     url = {https://CRAN.R-project.org/package=slam},
##   }
## 
## [[79]]
## To cite package 'glue' in publications use:
## 
##   Hester J, Bryan J (2024). _glue: Interpreted String Literals_. R
##   package version 1.7.0, <https://CRAN.R-project.org/package=glue>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {glue: Interpreted String Literals},
##     author = {Jim Hester and Jennifer Bryan},
##     year = {2024},
##     note = {R package version 1.7.0},
##     url = {https://CRAN.R-project.org/package=glue},
##   }
## 
## [[80]]
## To cite package 'Hmisc' in publications use:
## 
##   Harrell Jr F (2024). _Hmisc: Harrell Miscellaneous_. R package
##   version 5.1-3, <https://CRAN.R-project.org/package=Hmisc>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {Hmisc: Harrell Miscellaneous},
##     author = {Frank E {Harrell Jr}},
##     year = {2024},
##     note = {R package version 5.1-3},
##     url = {https://CRAN.R-project.org/package=Hmisc},
##   }
## 
## [[81]]
## The 'tools' package is part of R.  To cite R in publications use:
## 
##   R Core Team (2024). _R: A Language and Environment for Statistical
##   Computing_. R Foundation for Statistical Computing, Vienna, Austria.
##   <https://www.R-project.org/>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {R: A Language and Environment for Statistical Computing},
##     author = {{R Core Team}},
##     organization = {R Foundation for Statistical Computing},
##     address = {Vienna, Austria},
##     year = {2024},
##     url = {https://www.R-project.org/},
##   }
## 
## We have invested a lot of time and effort in creating R, please cite it
## when using it for data analysis. See also 'citation("pkgname")' for
## citing R packages.
## 
## [[82]]
## To cite package 'data.table' in publications use:
## 
##   Barrett T, Dowle M, Srinivasan A, Gorecki J, Chirico M, Hocking T
##   (2024). _data.table: Extension of `data.frame`_. R package version
##   1.15.4, <https://CRAN.R-project.org/package=data.table>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {data.table: Extension of `data.frame`},
##     author = {Tyson Barrett and Matt Dowle and Arun Srinivasan and Jan Gorecki and Michael Chirico and Toby Hocking},
##     year = {2024},
##     note = {R package version 1.15.4},
##     url = {https://CRAN.R-project.org/package=data.table},
##   }
## 
## [[83]]
## To cite package 'rhdf5' in publications use:
## 
##   Fischer B, Smith M, Pau G (2024). _rhdf5: R Interface to HDF5_.
##   doi:10.18129/B9.bioc.rhdf5 <https://doi.org/10.18129/B9.bioc.rhdf5>,
##   R package version 2.48.0, <https://bioconductor.org/packages/rhdf5>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {rhdf5: R Interface to HDF5},
##     author = {Bernd Fischer and Mike Smith and Gregoire Pau},
##     year = {2024},
##     note = {R package version 2.48.0},
##     url = {https://bioconductor.org/packages/rhdf5},
##     doi = {10.18129/B9.bioc.rhdf5},
##   }
## 
## [[84]]
## The 'grid' package is part of R.  To cite R in publications use:
## 
##   R Core Team (2024). _R: A Language and Environment for Statistical
##   Computing_. R Foundation for Statistical Computing, Vienna, Austria.
##   <https://www.R-project.org/>.
## 
## A BibTeX entry for LaTeX users is
## 
##   @Manual{,
##     title = {R: A Language and Environment for Statistical Computing},
##     author = {{R Core Team}},
##     organization = {R Foundation for Statistical Computing},
##     address = {Vienna, Austria},
##     year = {2024},
##     url = {https://www.R-project.org/},
##   }
## 
## We have invested a lot of time and effort in creating R, please cite it
## when using it for data analysis. See also 'citation("pkgname")' for
## citing R packages.
## 
## [[85]]
## To cite colorspace in publications use:
## 
##   Zeileis A, Fisher JC, Hornik K, Ihaka R, McWhite CD, Murrell P,
##   Stauffer R, Wilke CO (2020). "colorspace: A Toolbox for Manipulating
##   and Assessing Colors and Palettes." _Journal of Statistical
##   Software_, *96*(1), 1-49. doi:10.18637/jss.v096.i01
##   <https://doi.org/10.18637/jss.v096.i01>.
## 
## If you use HCL-based color palettes, please cite:
## 
##   Zeileis A, Hornik K, Murrell P (2009). "Escaping RGBland: Selecting
##   Colors for Statistical Graphics." _Computational Statistics & Data
##   Analysis_, *53*(9), 3259-3270. doi:10.1016/j.csda.2008.11.033
##   <https://doi.org/10.1016/j.csda.2008.11.033>.
## 
## If you use HCL-based color palettes in meteorological visualizations,
## please cite:
## 
##   Stauffer R, Mayr GJ, Dabernig M, Zeileis A (2009). "Somewhere over
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##   Visualizations." _Bulletin of the American Meteorological Society_,
##   *96*(2), 203-216. doi:10.1175/BAMS-D-13-00155.1
##   <https://doi.org/10.1175/BAMS-D-13-00155.1>.
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##   Zeileis A, Croissant Y (2010). "Extended Model Formulas in R:
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##   T, Lang M, Simko V, Hornik K, Neal R, Bell K, de Queljoe M, Suruceanu
##   I, Denney B, Schumacher D, Chang W, Attali D, Chirico. M (2024).
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##     title = {{O}rchestrating high-throughput genomic analysis with {B}ioconductor},
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## [[96]]
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##   Pagès H (2024). _SparseArray: High-performance sparse data
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##   doi:10.18129/B9.bioc.SparseArray
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## [[99]]
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##   K.S Pollard, S. Dudoit, M.J. van der Laan (2005). Multiple Testing
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##   Bioconductor, R. Gentleman, V. Carey, W. Huber, R. Irizarry, S.
##   Dudoit (Editors). Springer (Statistics for Biology and Health
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##   Henry L, Wickham H (2023). _lifecycle: Manage the Life Cycle of your
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##     url = {https://CRAN.R-project.org/package=httr},
##   }

2 Data Import

asv_tax<-read_excel("asv_tax.xlsx")
cecum_asv_table<-read_excel("cecum_asv_table.xlsx") %>%
  column_to_rownames("ASV")
cecum_a_diversity<-read_excel("cecum_a_diversity.xlsx")
cecum_metadata<-read_excel("cecum_metadata.xlsx")
cecum_Family<-read_excel("cecum_Family.xlsx")
cecum_akker<-read_excel("cecum_akker.xlsx")
cecum_DMSO_BRB_table<-read_excel("cecum_DMSO_BRB_table.xlsx") %>%
  column_to_rownames("ASV")
cecum_DMSO_BRB_metadata<-read_excel("cecum_DMSO_BRB_metadata.xlsx")
cecum_glm_table<-read_excel("cecum_glm_table.xlsx") %>%
  column_to_rownames("ASV")
cecum_glm_metadata<-read_excel("cecum_glm_metadata.xlsx")
saliva_asv_table<-read_excel("saliva_asv_table.xlsx") %>%
  column_to_rownames("ASV")
saliva_a_diversity<-read_excel("saliva_a_diversity.xlsx")
saliva_metadata<-read_excel("saliva_metadata.xlsx")
saliva_Family<-read_excel("saliva_Family.xlsx")
saliva_akker<-read_excel("saliva_akker.xlsx")
saliva_enter<-read_excel("saliva_enter.xlsx")
saliva_DMSO_BRB_table<-read_excel("saliva_DMSO_BRB_table.xlsx") %>%
  column_to_rownames("ASV")
saliva_DMSO_BRB_metadata<-read_excel("saliva_DMSO_BRB_metadata.xlsx")
ASV_richness<-read_excel("ASV_richness.xlsx")

3 Cecum

3.1 Alpha Diversity

Fit Linear Models

cecum_a_diversity %>%
  mutate(Treatment=factor(Treatment, levels=c("DMSO","DBP","BRB","BRB+DBP"))) %>%
  ggplot(aes(x=Treatment, y=Diversity, fill=Treatment)) +
  geom_boxplot(outlier.alpha=0) +
  geom_jitter(shape=21, width=0.2, height=0) +
  ylab("ASV Richness") 

lm<-
cecum_a_diversity %>%
  aov(Diversity~BRB*DBP, data=.)
  
summary(lm)
##             Df Sum Sq Mean Sq F value   Pr(>F)    
## BRB          1  15568   15568  67.395 3.96e-07 ***
## DBP          1    442     442   1.913    0.186    
## BRB:DBP      1    192     192   0.832    0.375    
## Residuals   16   3696     231                     
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
TukeyHSD(lm)
##   Tukey multiple comparisons of means
##     95% family-wise confidence level
## 
## Fit: aov(formula = Diversity ~ BRB * DBP, data = .)
## 
## $BRB
##              diff       lwr       upr p adj
## Control-BRB -55.8 -70.20912 -41.39088 4e-07
## 
## $DBP
##             diff       lwr      upr     p adj
## DBP-Control  9.4 -5.009119 23.80912 0.1856768
## 
## $`BRB:DBP`
##                              diff       lwr       upr     p adj
## Control:Control-BRB:Control -62.0 -89.50153 -34.49847 0.0000433
## BRB:DBP-BRB:Control           3.2 -24.30153  30.70153 0.9868010
## Control:DBP-BRB:Control     -46.4 -73.90153 -18.89847 0.0009617
## BRB:DBP-Control:Control      65.2  37.69847  92.70153 0.0000238
## Control:DBP-Control:Control  15.6 -11.90153  43.10153 0.3943185
## Control:DBP-BRB:DBP         -49.6 -77.10153 -22.09847 0.0004971

3.2 Beta diversity

dists<-list()

dists$`Bray-Curtis`<-cecum_asv_table %>% subsample_table() %>% make_proportion() %>% t() %>% vegan::vegdist(method="bray")
## Subsampling feature table to 11805 , currently has  346  taxa.
## ...after subsampling there are 336 taxa with 38.59 % of reads retained from 20 of 20 samples.
adonis2(dists$`Bray-Curtis`~BRB*DBP, cecum_metadata[match(labels(dists$`Bray-Curtis`), cecum_metadata$SampleID),] %>% mutate(BRB=if_else(grepl("BRB", Treatment), "BRB","Control")) %>% mutate(DBP=if_else(grepl("DBP", Treatment), "DBP","Control")))  
## Permutation test for adonis under reduced model
## Terms added sequentially (first to last)
## Permutation: free
## Number of permutations: 999
## 
## adonis2(formula = dists$`Bray-Curtis` ~ BRB * DBP, data = cecum_metadata[match(labels(dists$`Bray-Curtis`), cecum_metadata$SampleID), ] %>% mutate(BRB = if_else(grepl("BRB", Treatment), "BRB", "Control")) %>% mutate(DBP = if_else(grepl("DBP", Treatment), "DBP", "Control")))
##          Df SumOfSqs      R2      F Pr(>F)    
## BRB       1  0.58546 0.28290 7.0556  0.001 ***
## DBP       1  0.09344 0.04515 1.1261  0.319    
## BRB:DBP   1  0.06296 0.03042 0.7587  0.631    
## Residual 16  1.32764 0.64153                  
## Total    19  2.06950 1.00000                  
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
pcos<-lapply(dists, ape::pcoa)

varexp<-
lapply(names(pcos), function(x){
  tmp<-
  pcos[[x]]$values %>%
    as.data.frame() %>%
    mutate(PC=1:nrow(.)) %>%
    mutate(Metric=x)
  if(grepl("Euclid", x)){
    tmp %>% dplyr::select(Metric, PC, VarianceExplained=Relative_eig) %>% return()
  } else {
      tmp %>% dplyr::select(Metric, PC, VarianceExplained=Rel_corr_eig) %>% return()
    }
} ) %>%
  do.call(bind_rows, .) %>%
  mutate(VarianceExplained=VarianceExplained*100) %>%
  group_by(Metric) %>%
  mutate(CumulativeVarianceExplained=cumsum(VarianceExplained)) %>%
  filter(PC<10)

interactive_table(varexp)
lapply(names(pcos), function(x){
    pcos[[x]]$vectors %>%
      as.data.frame() %>%
      rownames_to_column("SampleID") %>%
      mutate(Metric=x)
  }) %>%
    do.call(bind_rows, .) %>%
        left_join(cecum_metadata) %>%
      ggplot(aes(x=Axis.1, y=Axis.2, fill=BRB, shape=DBP,colors=BRB)) +
      geom_point() +
    scale_shape_manual(values=c(21,24)) +
    xlab("PC1 (28.1%)") +
    ylab("PC2 (15.7%)") +
  scale_fill_manual(values=c( '#1cbdc2',"#f3766e"))
## Joining with `by = join_by(SampleID)`

3.3 Taxonomic

cecum_Family %>%
  column_to_rownames("ASV") %>%
  taxa_barplot(., cecum_metadata, "Treatment")+
  xlab("")+
  ylab("Abundance (%)")

3.4 Aldex glm

covariates <- cecum_glm_metadata %>%
  dplyr::select(BRB,DBP) %>%
  as.data.frame()

mm <- model.matrix(~ BRB * DBP, covariates)
x <- aldex.clr(cecum_glm_table, mm, mc.samples=16, denom="all")
## checking for condition length disabled!
## using all features for denominator
## operating in serial mode
## Warning in aldex.clr.function(reads, conds, mc.samples, denom, verbose, :
## values are unreliable when estimated with so few MC smps
## computing center with all features
glm.test <- aldex.glm(x) %>%
  mutate(FDR_BRB=p.adjust(`model.BRBTRUE Pr(>|t|)`, method="BH")) 

glm.eff <- aldex.glm.effect(x)
## operating in serial mode
## sanity check complete
## rab.all  complete
## rab.win  complete
## rab of samples complete
## within sample difference calculated
## between group difference calculated
## group summaries calculated
## effect size calculated
## summarizing output
## operating in serial mode
## sanity check complete
## rab.all  complete
## rab.win  complete
## rab of samples complete
## within sample difference calculated
## between group difference calculated
## group summaries calculated
## effect size calculated
## summarizing output
## operating in serial mode
## sanity check complete
## rab.all  complete
## rab.win  complete
## rab of samples complete
## within sample difference calculated
## between group difference calculated
## group summaries calculated
## effect size calculated
## summarizing output
glm.eff$BRBTRUE %>%
  as.data.frame() %>%
  mutate(ASV=rownames(.)) %>%
  left_join(glm.test %>% as.data.frame() %>% mutate(ASV=rownames(.)) ) %>%
  left_join(asv_tax) %>%
  mutate(Annot=if_else(`FDR_BRB`<0.1, paste(Genus, Species), "")) %>%
  mutate(Sig=if_else(`FDR_BRB`<0.1, "FDR<0.1", "ns")) %>%
  mutate(diff.btw=diff.btw) %>%
  ggplot(aes(x=diff.btw, y=-log10(`model.BRBTRUE Pr(>|t|)`), fill=Sig,label=Annot)) +
   scale_fill_manual(values=c("indianred","grey50")) +
  geom_text(size=2,color="black") +
  geom_jitter(shape=21, width=0.2, height=0,color="black")+
  xlab("log2(Fold Change)")+
  ylab("-log10(P-value)")
## Joining with `by = join_by(ASV)`
## Joining with `by = join_by(ASV)`

3.5 Differential abundance between BRB and DMSO

ald<-ALDEx2::aldex(cecum_DMSO_BRB_table, as.vector(cecum_DMSO_BRB_metadata$Treatment), include.sample.summary = TRUE) 
## aldex.clr: generating Monte-Carlo instances and clr values
## operating in serial mode
## computing center with all features
## aldex.ttest: doing t-test
## aldex.effect: calculating effect sizes
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.77086807586966, : provided 172 variables to replace 1 variables
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.77086807586966, : provided 172 variables to replace 1 variables
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.77086807586966, : provided 172 variables to replace 1 variables
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.77086807586966, : provided 172 variables to replace 1 variables
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.77086807586966, : provided 172 variables to replace 1 variables
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.77086807586966, : provided 172 variables to replace 1 variables
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.77086807586966, : provided 172 variables to replace 1 variables
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.77086807586966, : provided 172 variables to replace 1 variables
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.77086807586966, : provided 172 variables to replace 1 variables
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.77086807586966, : provided 172 variables to replace 1 variables
ald %>%
  interactive_table()
ald %>%
  rownames_to_column("ASV") %>%
  left_join(asv_tax) %>%
  mutate(Annot=if_else(we.eBH<0.1, paste(Genus, Species), "")) %>%
  mutate(Sig=if_else(we.eBH<0.1, "FDR<0.1", "ns")) %>%
  mutate(diff.btw=0-diff.btw) %>%
  ggplot(aes(x=diff.btw, y=-log10(we.ep), fill=Sig,label=Annot)) +
   scale_fill_manual(values=c("indianred","grey50")) +
  geom_text(size=2,color="black") +
  geom_jitter(shape=21, width=0.2, height=0,color="black")+
  xlab("log2(Fold Change)")+
  ylab("-log10(P-value)")
## Joining with `by = join_by(ASV)`

## Akkermansia

cecum_akker %>%
  mutate(Treatment=factor(Treatment, levels=c("DMSO","DBP","BRB","BRB+DBP"))) %>%
  ggplot(aes(x=Treatment, y=value, fill=Treatment)) +
  geom_boxplot(outlier.alpha=0) +
  geom_jitter(shape=21) +
  ylab("Akkermansia Abundance (CLR)")

fit<-
 cecum_akker %>%
  aov(value~BRB*DBP, data=.)

summary(fit)
##             Df Sum Sq Mean Sq F value   Pr(>F)    
## BRB          1  86.58   86.58  81.411 1.13e-07 ***
## DBP          1   1.50    1.50   1.411    0.252    
## BRB:DBP      1   1.02    1.02   0.956    0.343    
## Residuals   16  17.02    1.06                     
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
TukeyHSD(fit)
##   Tukey multiple comparisons of means
##     95% family-wise confidence level
## 
## Fit: aov(formula = value ~ BRB * DBP, data = .)
## 
## $BRB
##                 diff    lwr      upr p adj
## Control-BRB 4.161163 3.1835 5.138827 1e-07
## 
## $DBP
##                   diff       lwr       upr     p adj
## DBP-Control -0.5478155 -1.525479 0.4298481 0.2522276
## 
## $`BRB:DBP`
##                                    diff       lwr       upr     p adj
## Control:Control-BRB:Control  4.61205781  2.746070  6.478046 0.0000144
## BRB:DBP-BRB:Control         -0.09692095 -1.962909  1.769067 0.9987791
## Control:DBP-BRB:Control      3.61334782  1.747360  5.479336 0.0002372
## BRB:DBP-Control:Control     -4.70897876 -6.574967 -2.842991 0.0000111
## Control:DBP-Control:Control -0.99870998 -2.864698  0.867278 0.4430318
## Control:DBP-BRB:DBP          3.71026878  1.844281  5.576257 0.0001784

4 Saliva

4.1 Alpha Diversity

saliva_a_diversity %>%
  mutate(Treatment=factor(Treatment, levels=c("DMSO","DBP","BRB","BRB+DBP"))) %>%
  ggplot(aes(x=Treatment, y=Diversity, fill=Treatment)) +
  geom_boxplot(outlier.alpha=0) +
  geom_jitter(shape=21, width=0.2, height=0) +
  ylab("ASV Richness") 

lm<-
saliva_a_diversity %>%
  aov(Diversity~BRB*DBP, data=.)
  
summary(lm)
##             Df Sum Sq Mean Sq F value Pr(>F)
## BRB          1    541   540.8   0.765  0.395
## DBP          1    157   156.8   0.222  0.644
## BRB:DBP      1     29    28.8   0.041  0.843
## Residuals   16  11304   706.5
TukeyHSD(lm)
##   Tukey multiple comparisons of means
##     95% family-wise confidence level
## 
## Fit: aov(formula = Diversity ~ BRB * DBP, data = .)
## 
## $BRB
##             diff      lwr     upr   p adj
## Control-BRB 10.4 -14.7988 35.5988 0.39456
## 
## $DBP
##             diff      lwr     upr     p adj
## DBP-Control -5.6 -30.7988 19.5988 0.6439197
## 
## $`BRB:DBP`
##                              diff       lwr      upr     p adj
## Control:Control-BRB:Control   8.0 -40.09493 56.09493 0.9633282
## BRB:DBP-BRB:Control          -8.0 -56.09493 40.09493 0.9633282
## Control:DBP-BRB:Control       4.8 -43.29493 52.89493 0.9915633
## BRB:DBP-Control:Control     -16.0 -64.09493 32.09493 0.7778550
## Control:DBP-Control:Control  -3.2 -51.29493 44.89493 0.9974498
## Control:DBP-BRB:DBP          12.8 -35.29493 60.89493 0.8704676

4.2 Beta diversity

dists<-list()

dists$`Bray-Curtis`<-saliva_asv_table %>% subsample_table() %>% make_proportion() %>% t() %>% vegan::vegdist(method="bray")
## Subsampling feature table to 4304 , currently has  564  taxa.
## ...after subsampling there are 530 taxa with 13.44 % of reads retained from 20 of 20 samples.
adonis2(dists$`Bray-Curtis`~BRB*DBP, saliva_metadata[match(labels(dists$`Bray-Curtis`), saliva_metadata$SampleID),] %>% mutate(BRB=if_else(grepl("BRB", Treatment), "BRB","Control")) %>% mutate(DBP=if_else(grepl("DBP", Treatment), "DBP","Control")))  
## Permutation test for adonis under reduced model
## Terms added sequentially (first to last)
## Permutation: free
## Number of permutations: 999
## 
## adonis2(formula = dists$`Bray-Curtis` ~ BRB * DBP, data = saliva_metadata[match(labels(dists$`Bray-Curtis`), saliva_metadata$SampleID), ] %>% mutate(BRB = if_else(grepl("BRB", Treatment), "BRB", "Control")) %>% mutate(DBP = if_else(grepl("DBP", Treatment), "DBP", "Control")))
##          Df SumOfSqs      R2      F Pr(>F)  
## BRB       1   0.6523 0.12357 2.6123  0.024 *
## DBP       1   0.3262 0.06180 1.3065  0.244  
## BRB:DBP   1   0.3051 0.05779 1.2218  0.309  
## Residual 16   3.9952 0.75684                
## Total    19   5.2788 1.00000                
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
pcos<-lapply(dists, ape::pcoa)

varexp<-
lapply(names(pcos), function(x){
  tmp<-
  pcos[[x]]$values %>%
    as.data.frame() %>%
    mutate(PC=1:nrow(.)) %>%
    mutate(Metric=x)
  if(grepl("Euclid", x)){
    tmp %>% dplyr::select(Metric, PC, VarianceExplained=Relative_eig) %>% return()
  } else {
      tmp %>% dplyr::select(Metric, PC, VarianceExplained=Rel_corr_eig) %>% return()
    }
} ) %>%
  do.call(bind_rows, .) %>%
  mutate(VarianceExplained=VarianceExplained*100) %>%
  group_by(Metric) %>%
  mutate(CumulativeVarianceExplained=cumsum(VarianceExplained)) %>%
  filter(PC<10)

interactive_table(varexp)
lapply(names(pcos), function(x){
    pcos[[x]]$vectors %>%
      as.data.frame() %>%
      rownames_to_column("SampleID") %>%
      mutate(Metric=x)
  }) %>%
    do.call(bind_rows, .) %>%
        left_join(saliva_metadata) %>%
      ggplot(aes(x=Axis.1, y=Axis.2, fill=BRB, shape=DBP,colors=BRB)) +
      geom_point() +
    scale_shape_manual(values=c(21,24)) +
    xlab("PC1 (29.1%)") +
    ylab("PC2 (18.2%)") +
  scale_fill_manual(values=c( '#1cbdc2',"#f3766e"))
## Joining with `by = join_by(SampleID)`

4.3 Taxonomic

saliva_Family %>%
  column_to_rownames("ASV") %>%
  taxa_barplot(.,saliva_metadata, "Treatment")+
  xlab("")+
  ylab("Abundance (%)")

4.4 Differential abundance between BRB and DMSO

ald<-ALDEx2::aldex(saliva_DMSO_BRB_table, as.vector(saliva_DMSO_BRB_metadata$Treatment), include.sample.summary = TRUE) 
## aldex.clr: generating Monte-Carlo instances and clr values
## operating in serial mode
## computing center with all features
## aldex.ttest: doing t-test
## aldex.effect: calculating effect sizes
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.90294339517595, : provided 58 variables to replace 1 variables
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.90294339517595, : provided 58 variables to replace 1 variables
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.90294339517595, : provided 58 variables to replace 1 variables
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.90294339517595, : provided 58 variables to replace 1 variables
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.90294339517595, : provided 58 variables to replace 1 variables
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.90294339517595, : provided 58 variables to replace 1 variables
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.90294339517595, : provided 58 variables to replace 1 variables
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.90294339517595, : provided 58 variables to replace 1 variables
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.90294339517595, : provided 58 variables to replace 1 variables
## Warning in `[<-.data.frame`(`*tmp*`, , nm, value = structure(list(X1 =
## -2.90294339517595, : provided 58 variables to replace 1 variables
ald %>%
  interactive_table()
ald %>%
  rownames_to_column("ASV") %>%
  left_join(asv_tax) %>%
  mutate(Annot=if_else(we.eBH<0.1, paste(Genus, Species), "")) %>%
  mutate(Sig=if_else(we.eBH<0.1, "FDR<0.1", "ns")) %>%
  mutate(diff.btw=0-diff.btw) %>%
  ggplot(aes(x=diff.btw, y=-log10(we.ep), fill=Sig,label=Annot)) +
   scale_fill_manual(values=c("indianred","grey50")) +
  geom_text(size=2,color="black") +
  geom_jitter(shape=21, width=0.2, height=0,color="black")+
  xlab("log2(Fold Change)")+
  ylab("-log10(P-value)")
## Joining with `by = join_by(ASV)`

## Akkermansia

saliva_akker %>%
  mutate(Treatment=factor(Treatment, levels=c("DMSO","DBP","BRB","BRB+DBP"))) %>%
  ggplot(aes(x=Treatment, y=value, fill=Treatment)) +
  geom_boxplot(outlier.alpha=0) +
  geom_jitter(shape=21) +
  ylab("Akkermansia Abundance (CLR)")

fit<-
 saliva_akker %>%
  aov(value~BRB*DBP, data=.)

summary(fit)
##             Df Sum Sq Mean Sq F value  Pr(>F)   
## BRB          1 132.84  132.84  12.794 0.00252 **
## DBP          1   1.74    1.74   0.167 0.68782   
## BRB:DBP      1   6.40    6.40   0.616 0.44382   
## Residuals   16 166.12   10.38                   
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
TukeyHSD(fit)
##   Tukey multiple comparisons of means
##     95% family-wise confidence level
## 
## Fit: aov(formula = value ~ BRB * DBP, data = .)
## 
## $BRB
##                 diff      lwr      upr     p adj
## Control-BRB 5.154434 2.099594 8.209273 0.0025191
## 
## $DBP
##                   diff       lwr      upr     p adj
## DBP-Control -0.5896652 -3.644505 2.465174 0.6878197
## 
## $`BRB:DBP`
##                                   diff         lwr         upr     p adj
## Control:Control-BRB:Control  4.0229810  -1.8075458  9.85350794 0.2382864
## BRB:DBP-BRB:Control         -1.7211180  -7.5516449  4.10940893 0.8325378
## Control:DBP-BRB:Control      4.5647685  -1.2657584 10.39529543 0.1546746
## BRB:DBP-Control:Control     -5.7440990 -11.5746259  0.08642788 0.0542228
## Control:DBP-Control:Control  0.5417875  -5.2887394  6.37231438 0.9931580
## Control:DBP-BRB:DBP          6.2858865   0.4553596 12.11641339 0.0323974

4.5 Enterococcus_E

saliva_enter %>%
  mutate(Treatment=factor(Treatment, levels=c("DMSO","DBP","BRB","BRB+DBP"))) %>%
  ggplot(aes(x=Treatment, y=value, fill=Treatment)) +
  geom_boxplot(outlier.alpha=0) +
  geom_jitter(shape=21) +
  ylab("Enterococcus_E Abundance (CLR)")

fit<-
 saliva_enter %>%
  aov(value~BRB*DBP, data=.)

summary(fit)
##             Df Sum Sq Mean Sq F value  Pr(>F)   
## BRB          1  51.61   51.61   8.787 0.00913 **
## DBP          1  13.89   13.89   2.364 0.14370   
## BRB:DBP      1  17.47   17.47   2.974 0.10389   
## Residuals   16  93.98    5.87                   
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
TukeyHSD(fit)
##   Tukey multiple comparisons of means
##     95% family-wise confidence level
## 
## Fit: aov(formula = value ~ BRB * DBP, data = .)
## 
## $BRB
##                 diff       lwr      upr     p adj
## Control-BRB 3.212927 0.9152008 5.510652 0.0091349
## 
## $DBP
##                  diff       lwr       upr    p adj
## DBP-Control -1.666527 -3.964253 0.6311985 0.143697
## 
## $`BRB:DBP`
##                                   diff        lwr        upr     p adj
## Control:Control-BRB:Control  5.0820149  0.6965302  9.4674997 0.0204924
## BRB:DBP-BRB:Control          0.2025612 -4.1829236  4.5880459 0.9991397
## Control:DBP-BRB:Control      1.5463993 -2.8390855  5.9318840 0.7466494
## BRB:DBP-Control:Control     -4.8794537 -9.2649385 -0.4939690 0.0266585
## Control:DBP-Control:Control -3.5356157 -7.9211004  0.8498691 0.1380045
## Control:DBP-BRB:DBP          1.3438381 -3.0416467  5.7293228 0.8167634

5 ASV_richness

ASV_richness %>%
  pivot_longer(-AnimalID,names_to = "SampleType",values_to ="Diversity" ) %>%
  ggplot(aes(x=SampleType, y=Diversity, fill=SampleType)) +
  geom_boxplot(outlier.alpha=0) +
  geom_jitter(shape=21, width=0.2, height=0) +
  ylab("ASV Richness") 

ASV_richness%>%
  do(
    wilcox.test(.$cecum, .$saliva, paired=TRUE) %>%
      broom::tidy()
  ) %>%
  interactive_table()
## Warning in wilcox.test.default(.$cecum, .$saliva, paired = TRUE): cannot
## compute exact p-value with ties